Details of Protein

General Information of Protein (ID: PRT01128)
Name Ribosomal protein S6 kinase beta-1 (S6K1)
Synonyms   Click to Show/Hide Synonyms of This Protein
S6K-beta-1; S6K1; 70 kDa ribosomal protein S6 kinase 1; P70S6K1; p70-S6K 1; Ribosomal protein S6 kinase I; Serine/threonine-protein kinase 14A; p70 ribosomal S6 kinase alpha; p70 S6 kinase alpha; p70 S6K-alpha; p70 S6KA; RPS6KB1; STK14A
Gene Name RPS6KB1 Gene ID
6198
UniProt ID
P23443
Family Transferases (EC 2)
EC Number   EC: 2.7.11.1  (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Protein-serine/threonine kinases
EC: 2.7.11.1
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVG
PYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIF
AMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGEL
FMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLC
KESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKK
TIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEEL
LARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLE
SVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSG
IEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
Structure
3A60 ; 3A61 ; 3A62 ; 3WE4 ; 3WF5 ; 3WF6 ; 3WF7 ; 3WF8 ; 3WF9 ; 4L3J ; 4L3L ; 4L42 ; 4L43 ; 4L44 ; 4L45 ; 4L46 ; 4RLO ; 4RLP ; 5WBH ; 5WBK
Function Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Organic acids and derivatives
            Arginine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Arginine decrease (24 hours)
                      Induced Change RPS6KB1 protein abundance levels: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Brain cancer [ICD-11: 2A00]
                      Details It is reported that arginine decrease causes the decrease of RPS6KB1 protein abundance compared with control group.
            Glutamine Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Glutamine addition (1 hours)
                      Induced Change RPS6KB1 protein abundance levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that glutamine addition causes the increase of RPS6KB1 protein abundance compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Glutamine addition (96 hours)
                      Induced Change RPS6KB1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that glutamine addition causes the increase of RPS6KB1 protein phosphorylation compared with control group.
            Leucine Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Leucine decrease (24 hours)
                      Induced Change RPS6KB1 protein phosphorylation levels: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that leucine decrease causes the decrease of RPS6KB1 protein phosphorylation compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Leucine addition (1 hours)
                      Induced Change RPS6KB1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that leucine addition causes the increase of RPS6KB1 protein phosphorylation compared with control group.
References
1 Combinatory Treatment of Canavanine and Arginine Deprivation Efficiently Targets Human Glioblastoma Cells via Pleiotropic Mechanisms. Cells. 2020 Sep 30;9(10):2217.
2 Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009 Feb 6;136(3):521-34.
3 Regulation of protein turnover by L-glutamine in porcine intestinal epithelial cells. J Nutr Biochem. 2012 Aug;23(8):1012-7.
4 Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes. 2011 Mar;60(3):746-56.
5 Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol. 2007 Jul 15;582(Pt 2):813-23.

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